Yoshihiro Tani

Skin autofluorescence is associated with severity of vascular complications in Japanese patients with Type 2 diabetes.

Diabet. Med. 29, 492–500 (2012)

Skin autofluorescence is associated with renal function and cardiovascular diseases in pre-dialysis chronic kidney disease patients

BACKGROUND Tissue accumulation of advanced glycation end-products (AGE) is thought to be a contributing factor to the progression of cardiovascular disease (CVD). Skin autofluorescence, a non-invasive measure of AGE accumulation using autofluorescence of the skin under ultraviolet light, has shown associations with CVD in haemodialysis patients. The present study aimed to evaluate relationships of skin autofluorescence to renal function as well as CVD in pre-dialysis patients with chronic kidney disease (CKD). METHODS Subjects in this cross-sectional analysis comprised 304 pre-dialysis CKD patients [median age, 62.0 years; median estimated glomerular filtration rate (eGFR), 54.3 mL/min/1.73 m(2); diabetes, n = 81 (26.6%)]. AGE accumulation in skin was assessed by skin autofluorescence using an autofluorescence reader. Relationships between skin autofluorescence, eGFR, CVD history and other parameters were evaluated. RESULTS Skin autofluorescence correlated negatively with eGFR (r = -0.42, P < 0.01) and increased as CKD stage advanced. Multiple regression analysis revealed significant correlations of skin autofluorescence with age, presence of diabetes, eGFR and CVD history in CKD patients (R(2) = 30%). Age, male gender, smoking history, skin autofluorescence and eGFR were significantly correlated with CVD history, and multiple logistic regression analysis identified age [odds ratio (OR), 1.09; 95% confidence interval (CI), 1.03-1.15; P < 0.01], history of smoking (OR, 6.50; 95%CI, 1.94-21.83; P < 0.01) and skin autofluorescence (OR, 3.74; 95%CI, 1.54-9.24; P < 0.01) as independent factors. CONCLUSIONS Tissue AGE accumulation measured as skin autofluorescence increased as GFR decreased and was related to CVD history in CKD patients. Non-invasive autofluorescence readers may provide potential markers for clinical risk assessment in pre-dialysis CKD patients.

Skin Autofluorescence Is Associated with the Progression of Chronic Kidney Disease: A Prospective Observational Study

Background Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD). Methods Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis. Results Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004). Conclusions Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD.

The Great East Japan Earthquake: Blood Pressure Control in Patients With Chronic Kidney Disease

BACKGROUND At 1446 on 11 March 2011, northeastern Japan was struck by a major earthquake measuring 9.0 on the Richter scale. There have been several reports of transient blood pressure increases after a major earthquake, but the impact of a major earthquake on blood pressure in chronic kidney disease (CKD) patients has not been fully investigated. METHODS Changes in clinic blood pressure following the earthquake were investigated in 132 hypertensive patients with stage 3 and 4 CKD who were residents of Fukushima City. RESULTS Both systolic and diastolic blood pressures were significantly elevated 1-3 weeks after the earthquake compared with before the earthquake (134 ± 19 mm Hg vs. 138 ± 20 mm Hg, P = 0.02 for systolic; 76 ± 13 mm Hg vs. 79 ± 12 mm Hg, P = 0.01 for diastolic), and these values returned to baseline by 5-7 weeks after the earthquake. Multiple logistic regression analysis identified male sex (odds ratio (OR), 0.35; 95% confidence interval (CI), 0.14-0.86; P = 0.02), mean blood pressure at baseline (OR, 0.92; 95% CI, 0.86-0.96; P < 0.01), and sympatholytic medications, such as α-blockers, β-blockers, or central sympatholytics (OR, 0.23; 95% CI, 0.07-0.76; P = 0.01), as independent factors related to elevation of mean blood pressure 1-3 weeks after the earthquake in CKD patients. CONCLUSIONS Blood pressure was significantly increased after a major earthquake in hypertensive patients with stage 3 and 4 CKD. During the first 3 weeks after the earthquake, blood pressure control was associated with the use of sympatholytic medications.

Blood pressure elevation in hemodialysis patients after the Great East Japan Earthquake

A major earthquake measuring 9.0 on the Richter scale struck northeastern Japan at 2:46 pm on 11 March 2011. Several reports have described transient increases in blood pressure after major earthquakes, but the impact of such increases on hemodialysis patients has not been reported. We retrospectively investigated changes in blood pressure and influencing factors in 205 patients (mean age 66.6±13.0 years; male 51.7%; median dialysis vintage 6.0 (2.0–11.0) years) on chronic dialysis at three dialysis centers in the affected area (Fukushima City) for 8 weeks after the earthquake. Pre-dialysis blood pressure was significantly elevated at 1 week after the earthquake compared with baseline (systolic vs. diastolic blood pressure: 153.1±20.2/80.1±13.5 vs. 148.6±20.0/77.5±12.8 mm Hg, P<0.001), similarly post-dialysis blood pressure was elevated for up to 8 weeks. Independent factors influencing changes in blood pressure after the earthquake comprised baseline blood pressure and α-blockers. The earthquake induced a significant elevation in blood pressure among patients on chronic dialysis, and activation of the sympathetic nervous system might at least in part be associated with the mechanism underlying this increase.

Home Blood Pressure Control After the Great East Japan Earthquake in Patients on Chronic Hemodialysis

At 14:46 on 11 March 2011, northeastern Japan was struck by a major earthquake measuring 9.0 on the Richter scale (the Great East Japan Earthquake). Several reports have suggested a transient blood pressure (BP) increase after a major earthquake, but its impact on BP in chronic dialysis patients has not been reported. In a retrospective review of 25 hemodialysis patients who were residents of Koriyama City, changes in the morning home BP after the earthquake were investigated. Home systolic and diastolic BPs were significantly elevated 1 week after the earthquake (158 ± 16 mm Hg vs. 151 ± 13 mm Hg, P < 0.01, for systolic; 81 ± 13 mm Hg vs. 78 ± 11 mm Hg, P = 0.01, for diastolic). Mean home BP 1 week after the earthquake was unchanged from baseline in patients treated with sympatholytics and/or renin‐angiotensin system (RAS) inhibitors. BP values returned to baseline by 4 weeks after the earthquake, but percent changes in mean BP were significantly greater even 2 weeks, 4 weeks, and 6 weeks after the earthquake in patients not treated with RAS inhibitors than in those treated with RAS inhibitors (2 weeks 7.0% ± 4.5% vs. 0.2% ± 5.0%, P < 0.01; 4 weeks 4.4% ± 5.9% vs. −1.8% ± 5.3%, P = 0.02; 6 weeks 4.6% ± 4.9% vs. −1.9% ± 3.9%, P < 0.01). On multiple regression analysis, RAS inhibitor use had an independent relationship with percentage increases in mean BP during the 6 weeks after the earthquake. Home BP was significantly increased after a major earthquake in patients on chronic hemodialysis. Prolonged deterioration of BP control after the earthquake was associated with non‐use of RAS inhibitors.

The Relationship between Xanthine Oxidoreductase and Xanthine Oxidase Activities in Plasma and Kidney Dysfunction

Background: Oxidative stress (OS) is thought to play a role in detrimental events among patients with chronic kidney disease (CKD). Although the mechanism of OS increases in CKD patients is unclear, it has been suggested that increased activity of xanthine oxidase (XO), the superoxide-producing form of xanthine oxidoreductase (XOR), plays a large role in enhancing OS. Therefore, we measured the activities of plasma XOR and XO among CKD patients. Methods: Thirteen CKD patients were enrolled in this study. Their plasma XOR and XO activities were measured using a liquid chromatography-triple quadrupole mass spectroscopy (LC-TQMS) method, and the ratio of XO to XOR (XO/XOR) was calculated. Results: The XOR and XO activities (pmol/h/mL plasma) were 8.30–58.2 and 9.15–40.8, and XO/XOR value was 0.698–1.240. Both XOR and XO showed positive correlation with estimated glomerular filtration rate (eGFR) (R=0.751, P=0.0020 and R=0.773, P=0.0031, respectively). On the other hand, XO/XOR showed negative correlation with eGFR (R=-0.614, P=0.0236). Conclusion: XOR and XO activities are decreased, and XO/XOR ratio is increased, in accordance with renal dysfunction. High XO/XOR ratio in advanced CKD patients might contribute to the elevation of OS.

Comparison of albuminuria test and urine test strip in Japanese hypertensive patients: AVA-E study.

BACKGROUND Albuminuria is thought to reflect generalized endothelial dysfunction. In hypertensive patients, albuminuria is related to the risk for cardiovascular disease (CVD) events. Thus, screening for albuminuria is critical for risk stratification in hypertensive patients. However, the actual state of albuminuria in Japanese patients without diabetes remains unclear due to insurance coverage. METHODS The CLINITEK microalb creatinine test® is a urine test paper that can assess albumin excretion corrected for urine creatinine levels in only 60 seconds without any special equipment. The semi-quantitative albuminuria test and urine proteinuria test were performed on 8,181 Japanese hypertensive patients, and the clinical significance of the test was evaluated by comparison with the urine test strip method. RESULTS Albumin creatinine ratio (ACR) < 30 mg/g creatinine, ACR 30 - 299 mg/g creatinine, and ACR ≥ 300 mg/g creatinine on the albuminuria test were present in 70.0%, 25.7%, and 4.3%, respectively, of patients with a negative urine protein test strip result. Furthermore, in patients with a negative urine protein test strip result, ACR ≥ 30 mg/g creatinine was independently associated with previous CVD (odds ratio: 1.25, 95% confidence interval: 1.00 - 1.57, p < 0.05) after adjustment for estimated glomerular filtration rate, age, sex, BMI, smoking, dyslipidemia, diabetes, and blood pressure categories on multivariate logistic regression analysis. CONCLUSIONS We considered that urine test strip was inadequate test to evaluate albuminuria. Easy and quick albuminuria test on the CLINITEK MICROALB CREATININE TEST might be useful test to risk stratification of hypertensive patients compared to urine test strip.

Relationship between Xanthine Oxidoreductase Redox and Oxidative Stress among Chronic Kidney Disease Patients

Xanthine oxidase (XO), an isoform of xanthine oxidoreductase (XOR), is thought to increase the cardiovascular burden among chronic kidney disease (CKD) patients via oxidative radical production. Plasma XOR redox, which is characterized by the ratio of XO to total XOR, changes under different oxidative conditions associated with kidney dysfunction. However, the relationship between plasma XOR redox and oxidative stress (OS) is unclear. Thus, we aimed to clarify whether OS is related to XOR redox. We used the redox state of human serum albumin (HSA) as a marker to investigate the status of OS in CKD patients. HSA is composed of human mercaptoalbumin (HMA), which possesses not oxidized cysteine residues, reversibly oxidized human nonmercaptoalbumin-1 (HNA-1), and strongly oxidized human nonmercaptoalbumin-2 (HNA-2). The subjects included 13 nondialysis patients (7 males and 6 females) with varying degrees of kidney function. We found that ƒ(HMA) was negatively (R = −0.692, P = 0.0071) and ƒ(HNA-1) was positively (R = 0.703, P = 0.0058) correlated with plasma XO/XOR. ƒ(HNA-2) showed no correlation with XO/XOR (R = 0.146, P = 0.6412), indicating that plasma XOR redox is not related to the irreversible oxidation of HSA. In conclusion, plasma XOR redox is closely related to HSA redox, particularly reversible oxidation of HSA.

Oral Ferric Citrate Hydrate Associated With Less Oxidative Stress Than Intravenous Saccharated Ferric Oxide

Introduction A recent study suggested that orally dosed ferric citrate hydrate (FC) corrects renal anemia in patients on hemodialysis (HD), suggesting biological differences in effects of iron supplementation using different routes of administration. To address this issue, the present study compared oral FC with i.v. saccharated ferric oxide (FO) in stable HD patients. Methods Participants comprised 6 patients administered 3 consecutive protocols in the first HD session of the week in a fasting state: nothing given, as control (C); oral load of FC (480 mg iron), and 5 minutes of i.v. FO (40 mg iron). Iron dynamics in the body and biological impact on redox-inflammation status during the study (6 hours) were examined. Results Significant increases in serum iron and transferrin saturation were seen with both FC and FO. Regarding total iron-binding capacity as the sum of serum iron and unsaturated iron-binding capacity, no changes were found in FC, whereas significant increases were seen in FO (appearance of non–transferrin-binding iron [NTBI]), despite the lower serum iron levels in FO. Compared with C, increases were seen in serum myeloperoxidase (oxidative marker) with accompanying significant decreases in thioredoxin (antioxidant) in FO, whereas no changes were found in FC. Conclusion Oral FC differs from i.v. FO in areas such as less NTBI generation and less induction of oxidative stress. The result indicates potential clinical benefits of oral FC in terms of iron supplementation for renal anemia in HD patients.